title: Renal impairment and clinical outcomes of Clostridium difficile infection in two randomized trials.
abstract: OBJECTIVE
  Patients with chronic kidney disease (CKD) have increased risk for Clostridium difficile infection (CDI) and for subsequent mortality. We determined the effect of CKD on response to treatment for CDI.
  
  
  METHODS
  This is a post hoc analysis of two randomized controlled phase 3 trials that enrolled patients with CDI. Patients received either fidaxomicin 200 mg b.i.d. or vancomycin 125 mg q.i.d. for 10 days. Univariate and multivariate analyses compared end points by treatment received and CKD stage.
  
  
  RESULTS
  At baseline, 27, 21, and 9% of the patients had stage 2 (60-89 ml/min/1.73 m(2)), stage 3 (30-59), and stage 4 or higher (<30) CKD. Cure rates were similar for normal (91%) and stage 2 CKD (92%), but declined to 80% for stage 3 and to 75% for stage 4 CKD (p < 0.001 for trend). Time to resolution of diarrhea (TTROD) increased with stage 3 and stage 4 CKD. CDI recurrence rates 4 weeks after treatment were 16, 20, 27, and 24% for normal, stage 2, stage 3, and stage 4 or higher CKD, respectively. Mortality increased with CKD stage. In multivariate analyses, stage 3 or higher CKD correlated with lower odds of cure, greater chance of recurrence, and lower odds of sustained response 28 days after treatment. Initial cure rates were similar in the vancomycin or fidaxomicin groups; however, the rate of recurrence was higher following vancomycin treatment independent of renal function. The presence of immunosuppression did not alter this effect.
  
  
  CONCLUSIONS
  Progressive CKD is associated with increased TTROD, lower cure rates, and higher recurrence rates with treatment of CDI.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA. kmullane@medicine.bsd.uchicago.edu
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Mullane
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Cornely
authors.forename: Derrick W
authors.initials: DW
authors.lastname: Crook
authors.forename: Yoav
authors.initials: Y
authors.lastname: Golan
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Louie
authors.forename: Mark A
authors.initials: MA
authors.lastname: Miller
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Josephson
authors.forename: Sherwood L
authors.initials: SL
authors.lastname: Gorbach
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000617:Aminoglycosides / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D016360:Clostridioides difficile; D004761:Enterocolitis, Pseudomembranous / Q000150:complications / Q000188:drug therapy*; D005260:Female; D000077732:Fidaxomicin; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D014640:Vancomycin; D000077732:Fidaxomicin